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目的利用指纹基因群(GES)分析技术挖掘现有公共芯片数据揭示锯齿型结直肠癌的预后和耐药特性。方法从基因表达谱数据储存公共平台(GEO)中下载4个有预后信息的结直肠癌表达谱芯片数据(GSE14333、GSE17538、GSE33113、GSE37892),用批间误差校正和单基因信息抽提等信息技术获得1个整合的表达谱队列(n=600)。获得锯齿型结直肠癌表达谱有关数据及相应特异性指纹基因群,并与前面的表达谱队列合并,建立指纹基因群评分系统,依托已知锯齿型结直肠癌样本的基因群评分确定分组界值。根据分组界值,将600例结直肠癌分为锯齿型、过渡型和传统型结直肠癌组,利用Kaplan-Meier和Cox模型分析锯齿型结直肠癌的预后特征。同时,收集并下载与不可切除结直肠癌姑息治疗有关的表达谱数据(GSE28702、GSE5851),经表达谱数据抽提整理后,获得每个样本的锯齿型指纹基因群评分,通过比较治疗有效组和无效组之间评分的统计学差异来揭示锯齿型结直肠癌与药物耐药的关系。结果根据结直肠癌亚型评分界值,600个结直肠癌中有50个被分为锯齿型,126个被分类为过渡型,424个被分为传统型。锯齿型和过渡型结直肠癌与传统型结直肠癌相比具有几乎完全相同的预后能力,多因素Cox模型发现锯齿型和过渡型结直肠癌是患者术后复发的独立危险因素。单纯比较锯齿型和传统型结直肠癌,多因素Cox模型发现锯齿型结直肠癌是患者预后的不良因素(AHR=1.792,95%CI 1.011~3.177)。西妥昔治疗有效组的指纹基因群评分显著低于无效组(P=0.017),但FOLFOX治疗有效组和无效组的基因群评分无差异。结论结直肠癌锯齿型亚型是结直肠癌患者术后复发的独立危险因素,且与西妥昔单抗治疗耐药相关。
Objective To explore the prognosis and drug resistance of serrated colorectal cancer by using the fingerprinting gene cluster (GES) analysis technology to discover the existing public chip data. Methods Four colorectal cancer microarray data (GSE14333, GSE17538, GSE33113, GSE37892) with prognostic information were downloaded from the Gene Expression Data Storage Public Platform (GEO). Inter-assay error correction and single gene information extraction Technology to obtain one integrated expression profile queue (n = 600). Obtained zigzag colorectal cancer expression profiles and corresponding specific fingerprinting gene pool, and in front of the expression spectrum of the queue merger, the establishment of fingerprint gene cluster scoring system, relying on known serrated colorectal cancer samples of the gene group score to determine the group boundaries value. According to the dividing threshold, 600 cases of colorectal cancer were divided into serrated, transitional and traditional colorectal cancer groups. The prognostic characteristics of serrated colorectal cancer were analyzed by Kaplan-Meier and Cox models. At the same time, we collected and downloaded the expression data (GSE28702, GSE5851) related to the palliative treatment of unresectable colorectal cancer. After extraction and expression profile data extraction, the zigzag fingerprinting score of each sample was obtained. And invalid group scores between the statistical differences to reveal the relationship between serrated colorectal cancer and drug resistance. Results According to the colorectal cancer subtype rating threshold, 50 out of 600 colorectal cancers were classified as zigzag type, 126 as transitional type and 424 as traditional type. Zigzag and transitional colorectal cancer have almost identical prognostic power compared with traditional colorectal cancer. Multivariate Cox model found that serrated and transitional colorectal cancer are independent risk factors for postoperative recurrence. Compared with serrated type and traditional type of colorectal cancer, the multivariate Cox model found that serrated colorectal cancer was a negative prognostic factor (AHR = 1.792, 95% CI 1.011-3.1777). Cetuximab-treated group had significantly lower fingerprinting than that of the ineffective group (P = 0.017), but there was no difference in the gene group score between the FOLFOX-treated and the null-treated groups. Conclusions Sawtooth subtype of colorectal cancer is an independent risk factor for recurrence in patients with colorectal cancer and is associated with drug resistance of cetuximab.